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PubMed2006

Microfluidic isolation of leukocytes from whole blood for phenotype and gene expression analysis.

Technologies that enable the isolation of cell subtypes from small samples of complex populations will greatly facilitate the implementation of proteomics and genomics to human diseases. Transcriptome analysis of blood requires the depletion of contaminating erythrocytes. We report an automated microfluidic device to rapidly deplete erythrocytes from whole blood via deionized water lysis and to collect enriched leukocytes for phenotype and genomic analyses. Starting with blood from healthy subjects, we demonstrate the utility of this microfluidic cassette and lysis protocol to prepare unstimulated leukocytes, and leukocytes stimulated ex vivo with Staphylococcal enterotoxin B, which mimics some of the cellular effects seen in patients with severe bacterial infections. Microarrays are used to assess the global gene expression response to enterotoxin B. The results demonstrate that this system can isolate unactivated leukocytes from small blood samples without any significant loss, which permits more information to be obtained from subsequent analysis, and will be readily applicable to clinical settings.

Cell Separation↗

PubMed2025

CD40 transcriptomic expression patterns across malignancies: implications for clinical trials of CD40 agonists.

BACKGROUND: CD40 is a T-cell co-stimulatory receptor targeted by next-generation immunotherapies. We conducted a pan-cancer transcriptome analysis of CD40, its ligand, and related immune markers to evaluate co-expression patterns and clinical outcomes. METHODS: We analyzed transcriptome data for CD40, its ligand, and other common checkpoints and co-stimulators (PD-1, PD-L1, PD-L2, CTLA-4, LAG-3, ICOS, CD27, CD28, OX40, and GITR). RNA expression was classified as high (75-100th percentile), moderate (25-74th), or low (0-24th) against a reference population of 735 previously tested solid tumors. RESULTS: Of 514 patients, 114 (22%) showed high, 247 (48%) moderate, and 153 (30%) low CD40 RNA expression. High CD40 expression was most frequent in liver and bile duct (42%), pancreatic (42%), and ovarian (40%) cancers. Both high CD40 and low-moderate CD40 ligand expression-potentially conducive to CD40 agonist therapy-was most frequent in ovarian (33%) and pancreatic (24%) cancer. In both UCSD (N = 514) and TCGA (N = 10,953) cohorts, high CD40 expression significantly correlated with high CD28 and GITR. High CD40 RNA levels were not prognostic for overall survival (OS) from metastatic disease (P = 0.2) (n = 272 immune checkpoint inhibitor (ICI)-naïve patients). High CD40 expression correlated with longer OS from immunotherapy initiation (n = 217 ICI-treated patients; P = 0.04, univariable analysis), but not multivariable analysis, suggesting it may not be an independent predictive biomarker. CONCLUSION: High CD40 expression correlated with liver and bile duct, pancreatic, and ovarian cancers, as well as with CD28 and GITR transcripts. Immune marker co-expression in individual patients merits further exploration for the development of CD40-based and other immunotherapy interventions.

Humans↗

PubMed2026

ceRNA network of lncRNAs and mRNAs in OSF-to-OSCC progression: Diagnostic biomarkers and functional pathways.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic potentially malignant disorder that can progress to oral squamous cell carcinoma (OSCC). Although dysregulated non-coding RNAs have been implicated in oral carcinogenesis, the competing endogenous RNA (ceRNA)-mediated regulatory mechanisms underlying OSF-to-OSCC progression remain poorly understood. This study aimed to identify candidate regulatory molecules and construct a putative lncRNA-miRNA-mRNA network associated with malignant transformation. METHODS: Publicly available microarray datasets (GSE117973 and GSE125866) were analyzed to identify differentially expressed genes between OSF and OSCC. Differentially expressed transcripts were classified into mRNAs and lncRNAs based on public transcript annotations. Highly correlated lncRNA-mRNA pairs were identified using Pearson correlation analysis and integrated with multiMiR-supported miRNA-mRNA interactions obtained from public databases to construct a putative ceRNA regulatory network. Functional characterization focused on apoptosis, epithelial-mesenchymal transition (EMT), and immune checkpoint-related pathways. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance, and selected biomarkers were externally validated using The Cancer Genome Atlas (TCGA) OSCC cohort. RESULTS: Integrated transcriptomic analysis identified several dysregulated mRNAs and lncRNAs associated with OSF-to-OSCC progression. Network analysis highlighted TBC1D3B, RREB1, TEAD3, SREBF1, TMEM41B, FOXK2, and KIAA1958 as prominent hub genes within the putative regulatory network. Functional analyses demonstrated significant associations with apoptosis-, EMT-, and immune checkpoint-related genes, suggesting potential involvement in multiple biological processes contributing to malignant transformation. Several hub genes exhibited strong diagnostic performance, with ROC analysis yielding AUC values ranging from 0.891 to 1.000, indicating excellent discrimination between OSF and OSCC samples. External validation using TCGA further supported the relevance of the identified biomarkers in OSCC. CONCLUSIONS: This study provides a comprehensive transcriptomic framework describing putative lncRNA-miRNA-mRNA regulatory interactions associated with OSF progression to OSCC. The identified hub genes and regulatory networks represent candidate biomarkers for early detection and provide a foundation for future mechanistic and experimental validation. As the proposed ceRNA interactions are computationally inferred, further biological validation is required before clinical application.

RNA, Long Noncoding↗

PubMed2006

Expressed sequence tags from Madagascar periwinkle (Catharanthus roseus).

The Madagascar periwinkle (Catharanthus roseus) is well known to produce the chemotherapeutic anticancer agents, vinblastine and vincristine. In spite of its importance, no expressed sequence tag (EST) analysis of this plant has been reported. Two cDNA libraries were generated from RNA isolated from the base part of young leaves and from root tips to select 9,824 random clones for unidirectional sequencing, to yield 3,327 related sequences and 1,696 singletons by cluster analysis. Putative functions of 3,663 clones were assigned, from 5,023 non-redundant ESTs to establish a resource for transcriptome analysis and gene discovery in this medicinal plant.

ATP-Binding Cassette Transporters↗

PubMed2025

An intermediate activation state primes Langerhans cell migration from the epidermis.

Langerhans cells (LCs) are a specialized subset of dendritic cells in the epidermis, forming a dense network that acts as a frontline defense through immune surveillance. Upon antigen uptake, LCs become activated and orchestrate subsequent immune responses by migrating to lymphatics. However, how transcriptional programs are regulated during activation and how LCs behave in vivo during this transition remain poorly understood. Here, we combine single-cell transcriptomic analysis and intravital imaging to reconstruct the activation trajectory of epidermal LCs. We present a high-resolution single-cell transcriptomic dataset of over 22,000 high-quality epidermal LCs in both homeostatic and injured conditions. We define specific LC subpopulations representing sequential activation stages, characterized at the level of pathways and transcription factors. Notably, we identify a distinct intermediate state that precedes their migration. Integrating our data with an external dataset from homeostatic and injured skin reveals that wound-specific, WNT-modulated fibroblasts are the primary source of C3, the central component of the complement cascade. Intravital imaging of C3-deficient mice demonstrated that C3 is essential for effective recruitment of activated LCs to wound sites. Together, our findings uncover a novel population of activated epidermal LCs and highlight complement signaling as a critical mediator of LC recruitment during skin injury.

Activation↗

PubMed2025

Distinct spatial transcriptomic patterns of substantia Nigra in Parkinson disease and Parkinsonian subtype of multiple system atrophy.

To investigate transcriptomic signatures of Parkinson's disease (PD) and the Parkinsonian subtype of Multiple System Atrophy (MSA-P) in substantia nigra pars compacta (SNpc), we conducted transcriptome analysis using in-situ hybridization on paraffin-embedded SNpc tissues from post-mortem brains. The study included 2 MSA-P patients, 2 PD patients, and 2 healthy controls (HC), with 12 regions of interest (ROIs) selected from the dorsal to ventral and medial to lateral aspects of the SNpc. A total of 72 ROIs from 6 participants were analyzed, and differentially expressed genes (DEGs) were identified by comparing MSA-P, PD and HC groups. The MSA-P group showed 88 upregulated DEGs and 326 downregulated DEGs (adjusted 𝑝<0.05) compared to HC. The downregulated DEGs were significantly enriched in pathways related to ribosomal translation, immune processes, mitochondrial function, and autophagy. Notably, the dorsomedial quadrant was uniquely linked to antigen presentation, while other quadrants showed downregulation of protein synthesis. The PD group exhibited 165 upregulated DEGs and 350 downregulated DEGs (adjusted 𝑝<0.05) compared to HC, with downregulated DEGs associated with ribosomal translation, mitochondrial function, and the ubiquitin-proteasome system. In both MSA-P and PD, the upregulated DEGs were not associated with any pathways or biological process in gene enrichment analysis. In network propagation analysis, amyloid precursor protein was the most significant network hub among DEGs in both MSA-P and PD. Comparing the transcriptomic signatures of SNpc between MSA-P and PD, we found immune/inflammation, mitochondrial function and neural signaling related genes were significantly downregulated in MSA-P compared to PD. Overall, the transcriptomic signature of the SNpc in MSA-P and PD revealed overlapping but distinct features, including alterations in protein synthesis, immune processes, mitochondrial function, and protein degradation systems. Future studies with larger cohorts and functional validation are needed to further elucidate these findings.

Humans↗

PubMed2026

Multi-omics integration uncovers adaptive responses of stomach and pyloric ceca to artificial feed in mandarin fish (Siniperca chuatsi).

The mandarin fish, as an obligate piscivore, is highly dependent on live bait, which restricts its intensive aquaculture. Although domestication has enabled it to partially accept formulated diets, the tissue-specific molecular adaptation mechanisms of its digestive tract to artificial feed remain unclear. In this study, we conducted an integrated analysis of mandarin fish fed with live bait or artificial diet for three weeks, combining growth performance evaluation, gastric histology, and paired transcriptomic and metabolomic analyses of the stomach and pyloric ceca. AD feeding significantly improved growth performance, while histological examination revealed marked hyperplasia of the gastric mucosa and disorganized fold structures. Transcriptomic analysis identified 5065 and 3381 differentially expressed genes in the stomach and pyloric ceca, respectively. In the stomach, the artificial diet induced a glutathione-dependent antioxidant response, accompanied by glycolytic reprogramming and coordinated upregulation of genes in the extracellular matrix (ECM)-receptor interaction signaling pathway, including those encoding collagen, laminin, and integrin. In the pyloric ceca, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation were broadly suppressed, whereas glycosaminoglycan degradation and lysosomal pathways were activated. Metabolomic analysis showed that gastric metabolites were enriched in vascular and inflammatory mediator pathways, while metabolites in the pyloric ceca were enriched in peroxisome proliferator-activated receptor (PPAR) signaling, sphingolipid signaling, and steroid hormone biosynthesis pathways. Following artificial diet feeding, integrated multi-omics analysis of the stomach revealed significant enrichment of pathways such as phospholipase D signaling, sphingolipid signaling, and arachidonic acid metabolism, accompanied by the accumulation of key metabolites including sphingosine-1-phosphate, 20-hydroxyeicosatetraenoic acid, and cellobiose. Integrated analysis of the pyloric ceca identified significantly altered pathways, including sphingolipid metabolism, alpha-linolenic acid metabolism, and glutathione metabolism, along with elevated levels of sphingosine-1-phosphate, sphingosine galactoside, and 9-hydroxy-12-oxo-10,15-octadecadienoic acid, as well as decreased glutathionylspermidine. These findings systematically unveil the tissue-specific molecular adaptation characteristics of the mandarin fish digestive tract in response to artificial feed, providing an important basis for understanding the molecular mechanisms of dietary adaptation in carnivorous fish and for optimizing artificial feed formulations.

Animals↗

PubMed2005

Yeast HAT1 and HAT2 deletions have different life-span and transcriptome phenotypes.

HAT-B is a yeast histone acetyltransferase composed of Hat1, Hat2 and Hif1 proteins. We demonstrate that a hat2 mutant or a hat1hat2 double mutant, but not a hat1 mutant, have an extended life-span. Transcriptome analysis shows that the single hat mutants are not very different from wild type. However, the comparison of the hat1 and hat2 transcriptomes shows that they are different. The hat1hat2 double mutant shows a transcriptional phenotype similar to that of the hat1 mutant but strongly enhanced. These results indicate that Hat2p could have additional functions in the cell to those of Hat1p.

Acetyltransferases↗

PubMed2005

Light, the circadian clock, and sugar perception in the control of lignin biosynthesis.

Experiments were undertaken to investigate some of the mechanisms that may function to regulate lignin biosynthesis (lignification) in Arabidopsis thaliana. Northern blot analyses revealed that several genes encoding enzymes involved in the synthesis of lignin monomers displayed significant changes in transcript abundance over a diurnal cycle. Northern blot analysis also suggested that some of the changes in diurnal transcript abundance were likely to be attributable to circadian regulation, whereas others were likely to be attributable to light perception. Comparison of circadian changes in transcript abundance of lignin biosynthetic genes between wild-type plants and the sex1 mutant, which is impaired in starch turnover, suggested that carbon availability related to starch turnover might determine the capacity to synthesize lignins. This hypothesis was supported by the observation that the sex1 mutant accumulated fewer lignins than wild-type plants. Consistent with the relationship between carbon availability and lignin accumulation, analysis of dark-grown wild-type A. thaliana seedlings uncovered a role for sugars in the regulation of lignin biosynthesis. Analysis of lignin accumulation, as determined by qualitative changes in phloroglucinol staining, suggested that metabolizable sugars positively influence the abundance of lignins. Transcriptome analysis supports the hypothesis that sugars are not merely a source of carbon skeletons for lignification, but they also function as a signal to enhance the capacity to synthesize lignins.

Arabidopsis↗

PubMed2026

Selective saccular plasticity under microgravity links peripheral transcriptomic remodeling to postflight vestibular dysfunction.

Long-duration exposure to microgravity disrupts human balance and spatial orientation, yet the molecular mechanisms underlying vestibular adaptation to spaceflight remain poorly understood. Here, we tested the hypothesis that the saccule, the primary gravity-sensing otolith organ, undergoes selective remodeling during spaceflight and contributes to transient postflight postural instability. Using a cross-species approach, we combined transcriptomic analysis of mouse otolith organs with physiological assessments in astronauts. Laser microdissection-based RNA sequencing of mouse otolith sensory epithelia after a 35-d spaceflight revealed pronounced, organ-specific transcriptomic remodeling in the saccule, whereas the utricle remained stable. Principal component and clustering analyses demonstrated that the saccular transcriptome shifted toward an utricle-like profile under microgravity, accompanied by changes in genes related to synaptic and neuronal function. Promoter motif analysis identified NFAT-associated transcriptional networks, suggesting Ca2+-dependent regulation of synaptic plasticity as a potential molecular substrate of gravity-dependent adaptation. In parallel, vestibular testing in astronauts following long-duration missions (157 to 328 d) revealed selective attenuation of saccule-mediated cervical vestibular-evoked myogenic potentials and increased postural sway immediately after return to Earth, while utricle-mediated responses and semicircular canal function were preserved. Both saccular function and postural stability recovered within approximately 10 d. Notably, early postflight postural instability was partially mitigated by noisy galvanic vestibular stimulation, consistent with stochastic resonance-mediated sensory enhancement. Together, these findings identify the saccule as a plastic gravity sensor and establish a mechanistic link between peripheral molecular remodeling and functional balance deficits after spaceflight, providing a framework for developing countermeasures to facilitate vestibular readaptation during human space exploration.

Animals↗

PubMed2005

Transcript profiling of Eucalyptus xylem genes during tension wood formation.

Tension wood formed in response to gravitational force is a striking example of the plasticity of angiosperm wood. In this study our goal was to characterize the early changes in gene expression during tension wood formation in Eucalyptus. Using cDNA array technology, transcript profiling of 231 genes preferentially expressed in differentiating Eucalyptus xylem was followed from 6 h to 1 wk of a tension time course of artificially bent Eucalyptus trees. 196 genes were differentially regulated between control and bent trees, some exhibiting distinctive expression patterns related to changes in secondary cell wall structure and composition. For instance, expression of a cellulose synthase gene was well correlated with the appearance of the G-layers. Cluster correlation analysis revealed differential regulation of lignin biosynthetic genes and may also be used to help infer the function of unknown gene products. Eucalyptus wood transcriptome analysis during tension wood formation not only provided new clues into the transcriptional regulatory network of genes preferentially expressed in xylem, but also highlighted candidate genes responsible for the genetic and environmentally induced variation of wood quality traits.

Biomechanical Phenomena↗

PubMed2003

Construction and usage of a onefold-coverage shotgun DNA microarray to characterize the metabolism of the archaeon Haloferax volcanii.

Haloferax volcanii is a moderately halophilic archaeon that can grow aerobically and anaerobically with a variety of substrates. We undertook a novel approach for the characterization of metabolic adaptations, i.e. transcriptome analysis with a onefold-coverage shotgun DNA microarray. A genomic library was constructed and converted into a polymerase chain reaction (PCR) product library, which was used to print two DNA microarrays, a 960-spot test array used for optimization of microarray analysis and a 2880-spot onefold-coverage array. H. volcanii cultures were shifted from casamino acid-based metabolism to glucose-based metabolism, and the transcriptome changes were analysed with the onefold-coverage array at five time points covering the transition phase and the onset of exponential growth with the new carbon source. About 10% of all genes were found to be more than 2.5-fold regulated at at least one time point. The genes fall into five clusters of kinetically co-regulated genes. For members of all five clusters, the results were verified by Northern blot analyses. The identity of the regulated genes was determined by sequencing. Many co-regulated genes encode proteins of common functions. Expected as well as a variety of unexpected findings allowed predictions about the central metabolism, the transport capacity and the cellular composition of H. volcanii growing on casamino acids and on glucose. The microarray analyses are in accordance with the growth rates and ribosome contents of H. volcanii growing on the two carbon sources. Analysis of the results revealed that onefold-coverage shotgun DNA microarrays are well suited to characterize the regulation of metabolic pathways as well as protein complexes in response to changes in environmental conditions.

Gene Expression Profiling↗

PubMed2026

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals↗

PubMed2026

Comparative transcriptomics reveals hormone signaling and MADS-box genes in divergent development of inflorescences and tendrils in grapevine lateral shoots.

Hormone signaling and MADS-box genes regulate grapevine tendril and inflorescence growth divergence, offering molecular insights for managing tendril growth. Grapevine (Vitis vinifera L.) tendrils and inflorescences are homologous organs; however, their divergent development has important agronomic consequences because excessive tendril growth increases vineyard management costs. To explore the regulatory mechanisms, we compared the inflorescence-prone cultivar 'Einset Seedless' (ENT) with the tendril-prone cultivar 'Pinot Noir' (PN) using anatomical observation, transcriptome analysis of specific tendril nodes, and functional characterization of MADS-box genes. ENT exhibited a higher flowering rate at tendril nodes 1-4 than PN. Transcriptome profiling of specific tendril nodes uncovered 549 differentially expressed genes (DEGs) through an intersection/exclusion strategy, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicating that hormone and mitogen-activated protein kinase (MAPK) signaling were the primary candidates driving the divergence. To assess the spatiotemporal dynamics of these DEGs, we performed Mfuzz clustering, which revealed that multiple expression trajectories were highly consistent with the flowering gradient across different ENT and PN nodes. Plant hormone signal transduction was the predominantly enriched pathway across all dynamic clusters, highlighting the centrality of phytohormones in this process. Guided by this transcriptional evidence, we measured endogenous zeatin and gibberellin (GA₃) contents in the nodal tissues. Remarkably, the zeatin-to-GA₃ ratio not only paralleled the flowering gradient but also correlated with the cluster expression trajectories, providing physiological evidence for a cytokinin-gibberellin interaction model governing organ divergence. Additionally, we analyzed the differentially expressed transcription factors among the DEGs and identified a MADS-box gene, FRUITFULL-LIKE (VvFUL-L), which was markedly upregulated in PN tendrils. Heterologous overexpression of VvFUL-L in arabidopsis promoted early flowering and reduced inflorescence branching, suggesting its potential role in regulating lateral meristem development and affecting tendril formation. Collectively, these findings establish that Hormone Signaling, particularly cytokinin-GA crosstalk, and MADS-box regulators, such as VvFUL-L, are key regulators of inflorescence versus tendril growth in grapevines, providing a basis for future molecular and breeding studies.

Vitis↗

PubMed2025

Genomic and Transcriptomic Landscape of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma: A Multicenter Study.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare indolent malignant neoplasm, which occurs almost exclusively in the liver or spleen and may arise from a common EBV-infected mesenchymal cell that differentiates along the follicular or fibroblastic dendritic cell pathway. Despite its rarity, it presents a pressing need for an improved understanding of its genetic underpinnings and potential treatment strategies for recurrent or disseminated cases. To address this, we conducted comprehensive whole-exome sequencing and transcriptome sequencing (mRNA-seq) analyses on 31 and 6 cases of EBV+ IFDCS, respectively, collected from multiple centers in China. We also compared the genetic features of EBV+ IFDCS with those of other EBV-associated malignancies. Our analyses revealed a relatively high somatic mutation rate and widespread copy number variations affecting the major histocompatibility complex-I/II in EBV+ IFDCS. Integrated mutational profiling identified key signaling pathways involved in epigenetic regulation, NF-κB signaling, RTK/RAS/PI(3)K, and the Hippo pathway. Furthermore, we identified several frequently altered genes that could serve as potential therapeutic targets in EBV+ IFDCS. Transcriptomic analysis unveiled significant upregulation of pathways related to virus infection, immune responses, and multiple immune checkpoint genes in EBV+ IFDCS. Comparative analysis demonstrated clear genetic distinctions between EBV+ IFDCS and other EBV-associated tumors. In conclusion, our study provides comprehensive insights into the unique genomic and transcriptomic landscape of EBV+ IFDCS. We have identified multiple genetic alterations that likely contribute to the development and progression of this malignancy. Our results suggest that targeted therapy and immune checkpoint inhibitors may hold promise as potential therapeutic approaches for patients with recurrent or disseminated EBV+ IFDCS.

Humans↗

PubMed2025

Growth-limiting drought increases sensitivity of Asian rice (Oryza sativa) leaves to heat shock through physiological and spatially distinct transcriptomic responses.

Growth-limiting droughts (GLD) impair tissue expansion and delay developmental transitions but are often not considered as stressors, as many physiological traits are only slightly altered relative to well-watered counterparts. Concurrently, cell size, biochemical makeup, and transcriptome profiles vary along the leaf blade in accordance with the partitioning of distinct functions to spatially defined regions of the leaf. This suggests that because different parts of the leaf have underlying differences in their transcriptome profiles, they might respond to GLD in distinctive ways. Moreover, how antagonistic stressors influence physiology and gene expression in different zones of leaves is an open question. In this study, we profiled growth, anatomy, and gas exchange in Asian rice (Oryza sativa) leaves developed in well-watered and GLD conditions, with or without a secondary heat shock. We dissected leaves into seven equal-length segments for transcriptome analysis in these conditions. We hypothesized that GLD would make the leaves more sensitive to heat shock and would disrupt the underlying heterogeneity of the leaf transcriptome. GLD plants were more strongly affected by heat shock with respect to gas exchange and the number and types of genes that were differentially expressed and that these differences varied along the leaf blade. We developed an eFP browser tool with these data to facilitate exploration and hypothesis testing. These findings show that even mild drought treatments are sufficient to impact responses to antagonistic stressors and that substantial within-organ variance exists with respect to stress responses.

Oryza↗

PubMed2006

Can the state of cancer chemotherapy resistance be reverted by epigenetic therapy?

BACKGROUND: Transcriptome analysis shows that the chemotherapy innate resistance state of tumors is characterized by: poorly dividing tumor cells; an increased DNA repair; an increased drug efflux potential by ABC-transporters; and a dysfunctional ECM. Because chemotherapy resistance involves multiple genes, epigenetic-mediated changes could be the main force responsible of this phenotype. Our hypothesis deals with the potential role of epigenetic therapy for affecting the chemotherapy resistant phenotype of malignant tumors. PRESENTATION OF THE HYPOTHESIS: Recent studies reveal the involvement of DNA methylation and histone modifications in the reprogramming of the genome of mammalian cells in cancer. In this sense, it can be hypothesized that epigenetic reprogramming can participate in the establishment of an epigenetic mark associated with the chemotherapy resistant phenotype. If this were correct, then it could be expected that agents targeting DNA methylation and histone deacetylation would by reverting the epigenetic mark induce a global expression profile that mirror the observed in untreated resistant cells. TESTING THE HYPOTHESIS: It is proposed to perform a detailed analysis using all the available databases where the gene expression of primary tumors was analyzed and data correlated with the therapeutic outcome to determine whether a transcriptome profiling of "resistance" is observed. Assuming an epigenetic programming determines at some level the intrinsic resistant phenotype, then a similar pattern of gene expression dictated by an epigenetic mark should also be found in cell acquiring drug resistance. If these expectations are meet, then it should be further investigated at the genomic level whether these phenotypes are associated to certain patterns of DNA methylation and chromatin modification. Once confirmed the existence of an epigenetic mark associated to either the intrinsic or acquired chemotherapy resistant phenotype, then a causal association should be investigated. These preclinical findings should also be tested in a clinical setting. IMPLICATIONS OF THE HYPOTHESIS: Our hypothesis on the ability of epigenetic therapy to revert the epigenetic changes leading to a transcritome profile that defines the resistant state will eventually be a more rational and effective way to treat malignant tumors.

Acetylation↗

PubMed2004

In-depth profiling of lysine-producing Corynebacterium glutamicum by combined analysis of the transcriptome, metabolome, and fluxome.

An in-depth analysis of the intracellular metabolite concentrations, metabolic fluxes, and gene expression (metabolome, fluxome, and transcriptome, respectively) of lysine-producing Corynebacterium glutamicum ATCC 13287 was performed at different stages of batch culture and revealed distinct phases of growth and lysine production. For this purpose, 13C flux analysis with gas chromatography-mass spectrometry-labeling measurement of free intracellular amino acids, metabolite balancing, and isotopomer modeling were combined with expression profiling via DNA microarrays and with intracellular metabolite quantification. The phase shift from growth to lysine production was accompanied by a decrease in glucose uptake flux, the redirection of flux from the tricarboxylic acid (TCA) cycle towards anaplerotic carboxylation and lysine biosynthesis, transient dynamics of intracellular metabolite pools, such as an increase of lysine up to 40 mM prior to its excretion, and complex changes in the expression of genes for central metabolism. The integrated approach was valuable for the identification of correlations between gene expression and in vivo activity for numerous enzymes. The glucose uptake flux closely corresponded to the expression of glucose phosphotransferase genes. A correlation between flux and expression was also observed for glucose-6-phosphate dehydrogenase, transaldolase, and transketolase and for most TCA cycle genes. In contrast, cytoplasmic malate dehydrogenase expression increased despite a reduction of the TCA cycle flux, probably related to its contribution to NADH regeneration under conditions of reduced growth. Most genes for lysine biosynthesis showed a constant expression level, despite a marked change of the metabolic flux, indicating that they are strongly regulated at the metabolic level. Glyoxylate cycle genes were continuously expressed, but the pathway exhibited in vivo activity only in the later stage. The most pronounced changes in gene expression during cultivation were found for enzymes at entry points into glycolysis, the pentose phosphate pathway, the TCA cycle, and lysine biosynthesis, indicating that these might be of special importance for transcriptional control in C. glutamicum.

Amino Acids↗